Chemistry Reference
In-Depth Information
Fig. 8.1
Representation of the supposed structure of HA-OSA aggregates showed as multi
microdomains of OSA aggregation points inside the HA entanglements (Reproduced with permis-
sion, copyright 2012 Elsevier [
51
])
substitution and the short length of the hydrophobic chains grafted, proposed the
formation of a multiphase nanoaggregate composed of entangled HA chains and a
dispersion of hydrophobic domains (Fig.
8.1
).
Recently Liu and colleagues have investigated micelles made by HA grafted
with octadecylamine (C18) and loaded with paclitaxel (PTX) [
52
]. This work
demonstrated how, introducing into the HA graft copolymer a folic acid portion,
micelles were capable of a dual specific targeting toward CD44 and folate receptor
overexpressing tumor cells. In particular, these authors employed a low molecular
weight HA (11 kDa) that was processed in DMF, reacting with the octadecylamine
at 60
C in the presence of EDCI and NHS as activators of the glucuronic COOH.
Folic acid (FA) was activated with DCC/NHS, and the obtained derivative was
linked to the
N
-acetylglucosaminic OH group. Changing opportunely reaction
conditions, a C18 functionalization ranging from 12.7 to 19.3 mol% and an FA
functionalization of 6.8 mol% were obtained. Also in this case, increased amounts
of hydrophobic chains linked produce more stable micelles with lower CMC
values. Derivatives HA-C18 and HA-FA-C18 bearing 19 % of C18 and 9.3 % of
FA produced micelles with a dimension of 175 and 191 nm, respectively, and a
negative zeta potential value. Micelles were efficiently loaded with paclitaxel
indeed employing a drug/carrier weight ratio ranging from 10 to 30; encapsulation
efficiencies of 80-90 % were obtained. In vitro cytotoxicity studies confirmed
higher activity toward CD44-overexpressing cells A549 (non-small cell lung
cancer) and MCF-7 (breast cancer cells), and moreover HA-C18 bearing FA
moieties was more active toward MCF-7 cell
lines expressing FA receptors
(see Fig.
8.2
).
